Quantitative Systems Pharmacology Modeling of FGF19 Pathway Using NAFLDsym Prospectively Predicted Liver Fat and Serum Biomarker Responses to MET409 in NASH Patients

Quantitative Systems Pharmacology Modeling of FGF19 Pathway Using NAFLDsym Prospectively Predicted Liver Fat and Serum Biomarker Responses to MET409 in NASH Patients

Authors: Yang K, Woodhead JL, Kenz Z, Generaux GT, Siler SQ
Conference: ASCPT
Keywords: FGF19, fibroblasts, NAFLDsym, NASH, nonalcoholic steatohepatitis (NASH), qsp, QSP modeling, QST, quantitative systems pharmacology (QSP), Quantitative Systems Toxicology (QST)
Software: NAFLDsym®
Division: Quantitative Systems Pharmacology (QSP)

Treatment of nonalcoholic steatohepatitis (NASH) is a significant unmet medical need. In this work...

Proof-of-concept Simulations Using BIOLOGXsym, a Novel Quantitative Systems Toxicology (QST) Modeling Platform for Predicting Biologics-induced Liver Injury (BILI), Recapitulate Clinically Observed Hepatotoxicity of GGF2

Proof-of-concept Simulations Using BIOLOGXsym, a Novel Quantitative Systems Toxicology (QST) Modeling Platform for Predicting Biologics-induced Liver Injury (BILI), Recapitulate Clinically Observed Hepatotoxicity of GGF2

Authors: Beaudoin J, Vernetti L, Taylor DL, Gough A, Clemens L, Battista C, Siler SQ, Shoda LKM, Howell BA, Yang K
Conference: ASCPT
Keywords: (v)LAMPS, BILI, biochemistry, biologics, BIOLOGXsym, biomarkers, biomimetic, clinical trials, gastroplus, GGF2, liver, Microphysiology systems, pathophysiology, QST, Quantitative Systems Toxicology (QST), treatment
Software: BIOLOGXsym, GastroPlus®
Division: Quantitative Systems Pharmacology (QSP)

While biologics continue to address various unmet medical needs, BILI can terminate clinical development...

Model-based meta-analysis of relapsing mouse model studies from the critical path to tuberculosis drug regimens initiative database

Model-based meta-analysis of relapsing mouse model studies from the critical path to tuberculosis drug regimens initiative database

Authors: Berg A, Clary J, Hanna D, Nuermberger E, Lenaerts A, Ammerman N, Ramey M, Hartley D, Hermann D
Publication: Antimicrobial Agents and Chemotherapy
Keywords: model-based meta-analysis, modeling and simulation, Mycobacterium, Mycobacterium tuberculosis, relapsing mouse model, tuberculosis

erculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb), remains a leading infectious disease-related cause of death worldwide, necessitating the development of new

Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria

Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria

Authors: Taft BR, Yokokawa F, Kirrane T, Mata AC, Huang R, Blaquiere N, Waldron G, Zou B, Simon O, Vankadara S, Chan WL, Ding M, Sim S, Straimer J, Guiguemde A, Lakshminarayana SB, Jain JP, Bodenreider C, Thompson C, Lanshoeft C, Shu W, Fang E, Qumber J, Chan K, Pei L, Chen YL, Schulz H, Abas SN, Ang X, Liu Y, Angulo-Barturen I, Jimenez-Diaz MB, Gamo, FJ, Crespo-Fernandez B, Rosenthal PJ, Tumwebaze P, Cooper RA, Campo B, Campbell S, Wagner J, Diagana TT, Sarko C
Publication: J Med Chem
Keywords: dose selection, fih, gastroplus, machine learning, mechanistic absorption, PBPK modeling, physiologically based pharmacokinetics
Software: GastroPlus®

A series of 5-aryl-2-amino-imidazothiadiazole (ITD) derivatives were identified by a phenotype-based high-throughput screening using a blood stage Plasmodium falciparum (Pf) growth inhibition assay.

High-Throughput Screening for Extracellular Inhibitors of the FLT3 Receptor Tyrosine Kinase Reveals Chemically Diverse and Druggable Negative Allosteric Modulators

High-Throughput Screening for Extracellular Inhibitors of the FLT3 Receptor Tyrosine Kinase Reveals Chemically Diverse and Druggable Negative Allosteric Modulators

Authors: Hany R, Leyris JP, Bret G, Mallié S, Sar C, Thouaye M, Hamze A, Provot O, Sokoloff P, Valmier J, Rognan D
Publication: ACS Chem Bio
Keywords: Fluorescence, inhibition, inhibitors, Peptides and proteins, receptors
Software: ADMET Predictor®
Therapeutic Areas: Oncology

Inhibiting receptor tyrosine kinases is commonly achieved by two main strategies targeting either the intracellular kinase domain by low molecular weight compounds or...

In vivo neurophysiological assessment of in silico predictions of neurotoxicity: Citronellal, 3,4-dichloro-1-butene, and benzyl bromoacetate

In vivo neurophysiological assessment of in silico predictions of neurotoxicity: Citronellal, 3,4-dichloro-1-butene, and benzyl bromoacetate

Authors: Jung GL, McDaniel KL, LoPachin RM, Geohagen BC, Smith A, Huffstickler M, Herr DW
Publication: Neurotoxicology
Keywords: animal testing, gastroplus, mechanistic absorption, pbk, PBPK modeling, pbtk, risk assessment, safety exposure, Toxicity
Software: GastroPlus®

Neurotoxicants may be widespread in the environment and can produce serious health impacts in the human population.

Clinical Pharmacokinetics and Pharmacodynamics of Esaxerenone, a Novel Mineralocorticoid Receptor Antagonist: A Review

Clinical Pharmacokinetics and Pharmacodynamics of Esaxerenone, a Novel Mineralocorticoid Receptor Antagonist: A Review

Authors: Janković SM, Jankovic SV
Publication: Eur J Drug Metab Pharmacokinet
Keywords: ddI, Drug-drug interactions, fih, first-in-human, gastroplus, gut metabolism, IVIVE, mechanistic absorption, PBPK modeling, physiologically based pharmacokinetics
Software: GastroPlus®

Esaxerenone is a selective, nonsteroidal, high-affinity mineralocorticoid receptor antagonist recently approved in Japan for the treatment of hypertension.

Potent Neutralization of Omicron and other SARS-CoV-2 Variants of Concern by Biparatopic Human VH Domains

Potent Neutralization of Omicron and other SARS-CoV-2 Variants of Concern by Biparatopic Human VH Domains

Authors: Chen C, Martinez DR, Marti MM, Schafer A, Cheng MH, Mannar D, Zhu X, Banerjee A, Sobolewski MD, Kim A, Treat BR, Castanha PMS, Enick N, McCormick KD, Liu X, Adams C, Hines MG, Sun Z, Chen W, Jacobs JL, Barratt-Boyes S, Mellors JW, Baric R, Bahar I, Dimitrov D, Subramaniam S, Saville J, Li W
Publication: bioRxiv
Keywords: biparatopic antibody, COVID-19, Omicron variant, SARS-CoV-2

The emergence of SARS-CoV-2 variants of concern (VOCs) requires the development of next-generation biologics that are effective against a variety of strains of the virus.